Thompson C, Blumenstock F A, Saba T M, Feustel P J, Kaplan J E, Fortune J B, Hough L, Gray V
Department of Biochemistry, Albany Medical College, New York 12208.
J Clin Invest. 1989 Oct;84(4):1226-35. doi: 10.1172/JCI114289.
In humans, plasma fibronectin decreases early after operative injury, burn, or trauma, followed by a rapid restoration with a secondary decline typically observed if such patients become septic. We determined the rate of plasma fibronectin and plasma fibrinogen synthesis in normal subjects and injured patients using a stable isotope incorporation technique with [15N]glycine. During a constant 14-h infusion of [15N]glycine, the enrichment of [15N]glycine in both the free plasma glycine precursor pool as well as the urinary hippurate pool was determined; the latter used as an estimate of intracellular hepatic precursor enrichment. [15N]Glycine enrichment in both plasma fibronectin and fibrinogen was also quantified. The synthesis rate (Js/V) expressed in micrograms per milliliter of plasma per hour and the fractional synthesis rate (FSR) expressed as percentage of the plasma pool produced per day were determined. In normal subjects, the FSR for plasma fibronectin using 15N enrichment into urinary hippurate was 35.35 +/- 1.46%/d, whereas the Js/V was 4.45 +/- 0.19 micrograms/ml plasma per h. In normal subjects, the FSR for plasma fibronectin using 15N enrichment into free plasma glycine was 14.73 +/- 0.63%/d, whereas the Js/V was 1.98 +/- 0.09 micrograms/ml plasma per h. Early (2-3 d) after burn injury, fibronectin synthesis was increased (Js/V = 5.74 +/- 0.36; P less than 0.05), whereas later after injury, fibronectin synthesis began to decline (Js/V = 3.52 +/- 0.24; P less than 0.05) based on 15N enrichment of urinary hippurate. In contrast, the Js/V and FSR of plasma fibrinogen, a well-documented acute-phase plasma protein, revealed a sustained elevation (P less than 0.05) after injury in both the trauma and burn patients. Thus, plasma fibronectin synthesis is elevated early postinjury, which may contribute to the rapid restoration of its blood level. However, once fibronectin levels have normalized, the synthesis of plasma fibronectin appears to decline.
在人类中,手术损伤、烧伤或创伤后早期血浆纤连蛋白会减少,随后会迅速恢复,但若此类患者发生脓毒症,则通常会出现继发性下降。我们使用[15N]甘氨酸稳定同位素掺入技术,测定了正常受试者和受伤患者血浆纤连蛋白和血浆纤维蛋白原的合成速率。在持续14小时输注[15N]甘氨酸期间,测定游离血浆甘氨酸前体池以及尿马尿酸池中的[15N]甘氨酸富集情况;后者用于估计细胞内肝脏前体的富集情况。还对血浆纤连蛋白和纤维蛋白原中的[15N]甘氨酸富集进行了定量。确定了以每小时每毫升血浆微克数表示的合成速率(Js/V)以及以每天产生的血浆池百分比表示的分数合成速率(FSR)。在正常受试者中,使用尿马尿酸中15N富集计算的血浆纤连蛋白FSR为35.35±1.46%/天,而Js/V为4.45±0.19微克/毫升血浆每小时。在正常受试者中,使用游离血浆甘氨酸中15N富集计算的血浆纤连蛋白FSR为14.73±0.63%/天,而Js/V为1.98±其0.09微克/毫升血浆每小时。烧伤后早期(2 - 3天),基于尿马尿酸中15N富集,纤连蛋白合成增加(Js/V = 5.74±0.36;P < 0.05),而受伤后期,纤连蛋白合成开始下降(Js/V = 3.52±0.24;P < 0.05)。相比之下,血浆纤维蛋白原(一种有充分记录的急性期血浆蛋白)的Js/V和FSR在创伤和烧伤患者受伤后均持续升高(P < 0.05)。因此,血浆纤连蛋白合成在受伤后早期升高,这可能有助于其血液水平的快速恢复。然而,一旦纤连蛋白水平恢复正常,血浆纤连蛋白的合成似乎会下降。